The recent development of the bacterial class 2 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) CRISPR/Cas systems as genome editing tools has provided unprecedented ease and simplicity to engineer site-specific endonucleases for eukaryotic genome modification. However, because each CRISPR/Cas system requires a specific protospacer adjacent motif (PAM) for target DNA binding, each system is limited to certain genomic sites. Although the currently most widespread adopted Streptococcus pyogenes Cas9 (SpyCas9) uses a frequently occurring PAM (5′-NGG-3′) for targeting, it is still excluded from many genomic sites lacking such a motif, since eukaryotic genomes, especially those of mammals and plants, are highly complex and heterogeneous in DNA sequence. Moreover, precision gene editing using homology-directed repair (HDR) or base editors such as dCas9/cytidine deaminase and dCas9/adenosine deaminase often requires a precise DNA binding position, even at the single base pair resolution, to achieve an optimal editing outcome. Therefore, there is a need to develop new CRISPR/Cas systems that use novel PAMs for targeting to increase genome coverage density.